Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents

Hirschel, Josephin; Vogel, Mandy; Baber, Ronny; Garten, Antje; Beuchel, Carl; Dietz, Yvonne; Dittrich, J; Körner, Antje; Kieß, Wieland; Ceglarek, Uta

doi:10.3390/metabo10040149

Cited by 23 publications

(25 citation statements)

References 43 publications

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“…The gender-specific pattern of creatinine was associated with greater increases in serum leucine, valine, glutamine and proline in boys. Our observations agree with a recent report on whole blood amino acid patterns in puberty from the LIFE Child Cohort by Hirschel et al ( 43 ). Serum creatinine is known to be affected by age, gender, ethnicity, dietary protein intake, and lean mass ( 44 ).…”

Section: Discussionsupporting

confidence: 94%

Contributions of Fat and Carbohydrate Metabolism to Glucose Homeostasis in Childhood Change With Age and Puberty: A 12-Years Cohort Study (EARLYBIRD 77)

Cominetti¹,

Hosking

Jeffery

et al. 2020

Front. Nutr.

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Puberty—a period when susceptibility to the onset of Type 2 diabetes (T2D) increases—is marked with profound physiological and metabolic changes. In the EarlyBird cohort, children who developed impaired fasting glycemia in adolescence already exhibited higher fasting blood glucose at 5 years of age, independent of their body mass index (BMI), suggesting that pubertal factors may modify existing predisposition. Understanding how the physiological changes during childhood influence glucose homeostasis and how the central energy metabolism may help deciphering the mechanisms that underlie the risk of developing T2D in children and adults. We investigated these associations by analyzing glycemic variations with molecular markers of central energy metabolism, substrate oxidation status and pubertal stages in the EarlyBird cohort. The EarlyBird study is a non-interventional, prospective cohort study, that recruited 307 healthy UK children at age 5, and followed them annually throughout childhood for 12 years. Longitudinal data on blood biochemistry, respiratory exchange ratio, and anthropometry, available from 150 children were integrated with fasting glycemia. The gradual rise in blood glucose during childhood associates with age-dependent changes in molecular processes and substrate oxidation status, namely (i) greater pre-pubertal fat utilization, ketogenesis, and fatty acid oxidation, and (ii) greater pubertal carbohydrate oxidation and glycolytic metabolism (Cori and Cahill Cycles) associated with different amino acid exchanges between muscle and other tissues (proline, glutamine, alanine). Since children's metabolic and nutritional requirements evolve during childhood, this study has potential clinical implications for the development of nutritional strategies for disease prevention in children.

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Section: Discussionsupporting

confidence: 94%

Contributions of Fat and Carbohydrate Metabolism to Glucose Homeostasis in Childhood Change With Age and Puberty: A 12-Years Cohort Study (EARLYBIRD 77)

Cominetti¹,

Hosking

Jeffery

et al. 2020

Front. Nutr.

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“…Most of the other targeted analyses have specifically targeted amino acids and carnitines. Hirschel et al 29 analyzed dried blood sorts collected from 2,191 German children aged between 3 months and 18 years. They report positive association with BMI z score with leucine, isoleucine, tyrosine, valine, free carnitine, alanine, proline, and hydroxyproline and negative associations with citrulline.…”

Section: Resultsmentioning

confidence: 99%

A systematic review of metabolomic studies of childhood obesity: State of the evidence for metabolic determinants and consequences

et al. 2021

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Summary Childhood obesity has become a global epidemic and carries significant long‐term consequences to physical and mental health. Metabolomics, the global profiling of small molecules or metabolites, may reveal the mechanisms of development of childhood obesity and clarify links between obesity and metabolic disease. A systematic review of metabolomic studies of childhood obesity was conducted, following Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, searching across Scopus, Ovid, Web of Science and PubMed databases for articles published from January 1, 2005 to July 8, 2020, retrieving 1271 different records and retaining 41 articles for qualitative synthesis. Study quality was assessed using a modified Newcastle–Ottawa Scale. Thirty‐three studies were conducted on blood, six on urine, three on umbilical cord blood, and one on saliva. Thirty studies were primarily cross‐sectional, five studies were primarily longitudinal, and seven studies examined effects of weight‐loss following a life‐style intervention. A consistent metabolic profile of childhood obesity was observed including amino acids (particularly branched chain and aromatic), carnitines, lipids, and steroids. Although the use of metabolomics in childhood obesity research is still developing, the identified metabolites have provided additional insight into the pathogenesis of many obesity‐related diseases. Further longitudinal research is needed into the role of metabolic profiles and child obesity risk.

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“…Interestingly, the highest quartile of DRI was comprised predominantly of men. The increased proportion of men in the highest quartile of DRI, compared to LP-IR, could be explained by the fact that both plasma concentrations of BCAA and dietary intake of BCAA-rich foods are higher in men [43,44]. Despite the fact that there is not a general consensus about what are the main determinants of circulating BCAA, some studies suggest that such differences may at least in part be attributed to differences in dietary patterns between men and women [45].…”

Section: Discussionmentioning

confidence: 99%

A metabolomic index based on lipoprotein subfractions and branched chain amino acids is associated with incident hypertension

Flores‐Guerrero

Connelly

Shalaurova

et al. 2021

European Journal of Internal Medicine

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The present study aims to evaluate the performance of the Diabetes Risk Index (DRI), a metabolomic index based on lipoprotein particles and branched chain amino acids, on the incidence of newly developed hypertension in a large community dwelling cohort. Methods: The DRI was calculated by combining 6 lipoprotein parameters [sizes of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), concentrations of large VLDL, small LDL, and large HDL particles], and the concentrations of valine and leucine. DRI scores were estimated in 4169 participants from the PREVEND prospective cohort. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident hypertension. Results: During a median follow-up of 8.6 years, 924 new hypertension cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI and incident hypertension with a hazard ratio (HR) per 1 SD increase of 1.45 (95% CI 1.36,1.54; p < 0.001). After additional adjustment for traditional risk factors, the HR remained significant (HR adj 1.21, 95% CI 1.10, 1.33, p <0.001). Likewise, subjects in the top quartile of DRI presented with a higher risk of hypertension (HR adj 1.64, 95% CI 1.28, 2.10, p <0.001). Furthermore, the net reclassification improvement assessment improved after the addition of DRI to a traditional risk model (p <0.001), allowing proper reclassification of 34% of the participants. Conclusion: Higher DRI scores were associated with an increased risk of incident hypertension. Such association was independent of traditional clinical risk factors for hypertension.

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Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents

Cited by 23 publications

References 43 publications

Contributions of Fat and Carbohydrate Metabolism to Glucose Homeostasis in Childhood Change With Age and Puberty: A 12-Years Cohort Study (EARLYBIRD 77)

Contributions of Fat and Carbohydrate Metabolism to Glucose Homeostasis in Childhood Change With Age and Puberty: A 12-Years Cohort Study (EARLYBIRD 77)

A systematic review of metabolomic studies of childhood obesity: State of the evidence for metabolic determinants and consequences

A metabolomic index based on lipoprotein subfractions and branched chain amino acids is associated with incident hypertension

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